Stent-containing medical devices and methods of using the same

ABSTRACT

The present disclosure pertains to medical devices that comprise a stent body having two ends, a central region therebetween, and comprising structural elements extending around the stent body and a covering material disposed over the stent body, the covering material covering only a portion of the stent body, in which the covering material is provided with a plurality of openings that provide areas where the stent body is not covered by the covering material. The present disclosure further pertains to medical apparatuses that comprise such medical devices and methods of treatment using such medical devices.

CROSS-REFERENCE APPLICATION

This application is a continuation of U.S. patent application Ser. No.16/802,178, filed Feb. 26, 2020, which is a continuation of U.S. patentapplication Ser. No. 14/753,201, filed Jun. 29, 2015, now U.S. Pat. No.10,610,386, which claims the benefit of priority under 35 U.S.C. § 119to U.S. Provisional Application Ser. No. 62/018,262 filed Jun. 27, 2014,the disclosures of which are herein incorporated herein by reference intheir entirety.

FIELD

The present invention relates to stent-containing medical devices and tomethods of treatment using the same.

BACKGROUND

A stent is a small mesh tube that is used to treat narrowed or weaklumens (e.g., an artery, vein, bile duct, esophagus, intestine, lung,etc.), for example, to counteract lumen constriction due to variousdiseases and conditions. Stents can be formed from metals, polymers orother suitable material. Stents can be biostable or bioresorbable, drugeluting or non-drug-eluting. The most common use for a stent is incoronary arteries. Other common types of stents besides coronary stentsinclude peripheral stents, ureteral stents (e.g., to ensure patency ofthe ureter), biliary stents (e.g., to treat obstruction in the bile orpancreatic duct), esophageal stents (e.g., to treat blockages of theesophagus), enteral stents (e.g., to treat blockage of the small bowelor colon), and airway stents (e.g., to treat blockage of the trachea orbronchi), among others.

In some cases, stents are covered. If the covering of the covered stentis porous, typically for use in the vasculature, it is often called astent-graft. Stent-grafts are used in the treatment of abdominal aorticaneurysms and weakened peripheral arteries. Other covered stents may beused for the treatment of malignant or benign strictures of theesophagus as well leaks and/or perforations in various body lumens,among other uses. In some cases covered stents are temporarily placedand are removable.

Fixation is extremely important in the placement of a stent, whethercovered, partially covered or non-covered, because if the implantmigrates, the treatment can be compromised and further complications canoccur.

As one specific example, placement of covered self-expanding metal orpolymer stents has been the first choice for palliative therapy ofunresectable esophageal cancer. These stents are also highly effectivefor the management of benign (peptic, postsurgical, corrosive)strictures, esophageal leaks, perforations and fistula. In most cases,rapid relief of dysphagia and adequate oral intake of nutrients can beachieved. If the stent migrates from the esophagus, such as into thestomach or small intestine causing an obstruction, the patient cansuffer severe pain and fever resulting in an additional surgery toremove the stent. The same also applies for other GI and airway stents.

As another specific example, abdominal aortic aneurysm (AAA)stent-grafts are often used to address arterial aneurysms, which arecharacterized by a weak artery wall. Over time, blood pressure and otherfactors can cause this weak area to bulge like a balloon and it caneventually enlarge and rupture. The AAA stent graft is designed to sealtightly with the artery above and below the aneurysm. The graft isstronger than the weakened artery and it allows blood to pass through itwithout pushing on the bulge. If the stent-graft were to migrate, theseal above the aneurysm may be compromised. This may result in bloodflowing into the aneurysmal sac causing it to grow and possible rupture.Re-intervention may be required.

SUMMARY

In accordance with some aspects of the present disclosure,stent-containing devices are provided which comprise an associatedbonding material, wherein the stent-containing device is configured tobond to a lumen when exposed to an energy source while thestent-containing device is in contact with the lumen.

In some aspects, the present disclosure features medical devicescomprising (a) a stent component, (b) an optional covering material, and(c) a bonding material associated with the stent component, the optionalcovering material, or both; wherein the medical device is configured tobe implanted a patient and to bond to adjacent patient tissue when thebonding material is exposed to energy from an energy source.

In certain embodiments, which may be used in combination with any of theabove aspects, the bonding material comprises a tissue solder material,the bonding material comprises a tissue solder and a photosensitizingdye, or the bonding material comprises a tissue solder and an energyabsorber.

In certain embodiments, which may be used in combination with any of theabove aspects and embodiments, the bonding material comprises a tissuesolder selected from chitosan, albumin, collagen, elastin, fibrinogen,nano-peptides, derivatives of the foregoing, and combinations of two ormore of the foregoing.

In certain embodiments, which may be used in combination with any of theabove aspects and embodiments, the bonding material comprises a tissuesolder and a photosensitizing dye selected from rose bengal dye,methylene blue dye, fluorescein dye, indocyanine green, basic fuchsin,fen, xanthane dye, riboflavin dye, lumichrome dye, flavin, lumiflavindye, Reactive Black 5 dye, and combinations of two or more of theforegoing.

In certain embodiments, which may be used in combination with any of theabove aspects and embodiments, the bonding material comprises a tissuesolder and an energy absorber selected from chromophores,superparamagnetic iron oxide nanoparticles (SPIONs), gold nanorods, goldnanoshells, gold nanocages and combinations of two or more of theforegoing.

In certain embodiments, which may be used in combination with any of theabove aspects and embodiments, the bonding material comprises a tissuesolder and a synthetic polymer selected from polylactic acid,polyglycolic acid, poly(lactic acid-co-glycolic acid), polydioxanone,polycaprolactone, and combinations of two or more of the foregoing.

In further aspects, which may be used in combination with any of theabove aspects and embodiments, the bonding material is associated withthe medical device (a) by a coating of the bonding material over atleast a portion of the stent component, the optional covering material,or both, (b) by integrating the bonding material into at least a portionof the stent component, the optional covering material, or both, or (c)a combination of the foregoing.

In further aspects, which may be used in combination with any of theabove aspects and embodiments, the bonding material is associated withthe ends of the medical device but not the center of the medical deviceor the bonding material is provided as a series of bands or islandsalong the length of the medical device.

In further aspects, which may be used in combination with any of theabove aspects and embodiments, the medical device comprises the optionalcovering material. The covering material may, for example, cover theentire stent component or cover only a portion of the stent component.For instance, in certain embodiments, only the ends of the stentcomponent may be covered by the covering material, or the coveringmaterial may be provided with a plurality of openings that provide areaswhere the stent component is not covered by the covering material. Incertain embodiments, the covering material covers only a portion of thestent component, and the bonding material is associated with the stentcomponent in areas of the stent component not covered by the coveringmaterial.

In further aspects, which may be used in combination with any of theabove aspects and embodiments, the medical device comprises the optionalcovering material, and the covering material is sufficiently transparentto the energy from the energy source such that bonding material that ispositioned abluminally relative to the covering material can beactivated using an energy source positioned luminally relative to thecovering material.

Other aspects of the present disclosure provide methods of attaching astent-containing medical device to a lumen, wherein energy from anenergy source is applied to a bonding material that is associated withthe stent-containing medical device, such that the bonding material isactivated and the stent-containing device is attached to the lumen. Incertain embodiments, stent-containing medical devices, such as thosedescribed in any of the above aspects and embodiments, are employed inthe method.

Yet other aspects of the present disclosure features kits that compriseany combination of any two or more of the following items: (a) astent-containing medical device comprising a stent component, anoptional covering, and an optional bonding material associated the stentcomponent, the optional covering, or both, (b) a bonding material insolid form or in fluid form, (c) a surgical device, either with orwithout an associated energy source, that is configured to receive andplace the medical device in a subject, (d) a guide wire, either with orwithout an associated energy source, or (e) a standalone energy source.In certain embodiments, stent-containing medical devices, such as thosedescribed in any of the above aspects and embodiments, are employed inthe kit.

An advantage of the present disclosure is that compositions, devices,kits and procedures are provided whereby stent-containing medicaldevices may be implanted in body lumens, accompanied by bonding materialactivation, such that migration of the devices within the body lumens isminimized or prevented after implantation.

Another advantage of the present disclosure is that compositions,devices, kits and procedures are provided whereby stent-containingmedical devices, particularly covered stents, may be implanted in bodylumens, accompanied by bonding material activation, such that thedevices are sealed with respect to the body lumens.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a solder-containing stent, inaccordance with an embodiment of the present disclosure.

FIG. 2 is a schematic illustration of a solder-containing stent, inaccordance with another embodiment of the present disclosure.

FIG. 3 is a schematic illustration of a solder-containing stents inaccordance with another embodiment of the present disclosure.

FIG. 4 is a schematic illustration of a solder-containing stent, inaccordance with another embodiment of the present disclosure.

FIG. 5A is a schematic illustration of a solder-containing stent, inaccordance with another embodiment of the present disclosure.

FIG. 5B is a schematic illustration of a solder-containing stent, inaccordance with another embodiment of the present disclosure.

FIG. 6 is a schematic illustration of a solder-containing stent, inaccordance with another embodiment of the present disclosure.

FIGS. 7A, 7B and 7C are schematic illustrations of a method ofimplanting a stent, in accordance with an embodiment of the presentdisclosure.

FIGS. 8A, 8B and 8C are schematic illustrations of a method ofimplanting a stent, in accordance with another embodiment of the presentdisclosure.

FIG. 9 is a schematic illustration of a method of implanting a stent, inaccordance with yet another embodiment of the present disclosure.

FIG. 10 is a schematic illustration of an energy-emitting device, inaccordance with an embodiment of the present disclosure.

FIG. 11 is a schematic illustration of an energy-emitting device, inaccordance with another embodiment of the present disclosure.

FIG. 12 is a schematic illustration of an energy-emitting device, inaccordance with another embodiment of the present disclosure.

DETAILED DESCRIPTION

The present disclosure pertains to methods, compositions, devices andkits that are useful in the implantation and fixation ofstent-containing medical devices, for example, bare stents, drug elutingstents, partially covered stents, and fully covered stents, amongothers, in a body lumen of a subject, typically a vertebrate subject,and more typically a mammalian subject, such as human subject, pet orlivestock. The devices may be implanted and fixed in a variety oflumens, for example, in a blood vessel (e.g., artery, vein etc.), alumen of the gastrointestinal tract (e.g., esophagus, stomach, duodenum,small intestine, large intestine, colon, biliary duct, etc.), aurogynecological lumen (e.g., ureter, urethra, fallopian tube, etc.), oran airway lumen (e.g. trachea, bronchi, etc.), among other lumens, forinstance, to prevent migration within the lumen and/or create a sealwith the lumen (e.g., in the case of a covered stent). In variousembodiments, stent-containing devices are used to provide one or more ofthe following functions: support the patency of the body lumen,strengthen the body lumen wall, seal the body lumen wall, and preventtissue ingrowth into the body lumen, among other functions.

According to one aspect, the present disclosure is directed tostent-containing devices that are configured for implantation in a bodylumen which comprise (a) a stent component, (b) an optional coveringmaterial and (c) a bonding material. The bonding material is associatedwith at least a portion of the stent-containing device (e.g., associatedwith the stent component, the optional covering, or both), such that thestent-containing devices are capable of bonding to adjacent patienttissue when exposed to an energy. For example, the bonding material maybe associated with the device by one or more of the followingstrategies, among others: (a) the bonding material may be coated ontoall or a portion of the stent component, (b) the bonding material may beintegrated into all or a portion of the stent component, (c) the bondingmaterial may be coated onto all or a portion of the optional coveringmaterial or (d) the bonding material may be integrated into all or aportion of the optional covering material.

The stent-containing device is introduced into a body lumen, forexample, a blood vessel, a lumen of the gastrointestinal tract, aurogynecological lumen, or an airway lumen, among others, using asuitable procedure. Energy is then applied to the bonding material suchthat that bonding material is activated and the stent-containing deviceis attached to the body lumen tissue.

Different energy sources may be used for device attachment, depending onthe mechanism for tissue bonding that is employed. The energy source maybe, for example, a source of heat or light, such as a laser or alight-emitting diode (LED). Infrared and near-infrared laser sourcesinclude carbon dioxide (CO₂), thulium-holmium-chromium, holmium,thulium, and neodymium rare-earth-doped-garnets (THC:YAG, Ho:YAG,Tm:YAG, and Nd:YAG, respectively), and gallium aluminum arsenide diode(GaAlAs) lasers, among others. Visible sources include potassium-titanylphosphate (KTP) frequency-doubled Nd:YAG, and argon lasers, amongothers. Other energy sources include radiofrequency sources (e.g., amicrowave source), radiation sources (e.g., x-ray radiation, gammaradiation, etc.), or a locally produced plasma. Argon plasmas arecurrently employed in various medical applications, including argon beamcoagulators, which ionize argon gas to form an argon plasma and then usethe plasma to deliver thermal energy to nearby tissue. In the presentdisclosure, an argon beam may be used as a source of heat for tissuebonding.

In certain embodiments, the energy source is provided in a stand-aloneunit. In other embodiments, the energy source is combined with anotherdevice. For example, the energy source may be combined with a deliverydevice, such as a guide wire or catheter.

In some embodiments, the energy source is connected to a control unit,which controls the energy emitting from the energy source. Preferably,the amount of energy is sufficient to activate the bonding materialwithout significantly damaging the underlying tissue. In someembodiments, the control unit is designed to accept user input (e.g.,via physical buttons, touchscreen, etc.), thereby allowing treatmentparameters to be set by a health care provider.

In some embodiments, the energy source is controlled without the use ofa sensor (e.g., based on the experience of the surgeon or based on asuitable energy output algorithm). In other embodiments, a sensor isused in conjunction with the energy source to provide feedback regardingthe amount of energy being directed to the bonding site, and thisfeedback can be used to adjust the energy source output. For example, incertain embodiments, the sensor is a temperature sensor which detectsthe amount of heat at the bonding site. In these embodiments, suitablesoftware can be employed to adjust the output of the energy source basedon input from the temperature sensor. The sensor may be provided, forexample, in the same device as the energy source or in a device that isdifferent from the device containing the energy source. The sensor maybe provided, for example, in a medical device that is used for devicedelivery (either with or without the energy source).

A variety of bonding materials can be used in conjunction with thepresent disclosure.

In this regard, laser tissue soldering processes are known in thesurgical art whereby tissue is bonded by applying a solder (commonly, abiological polymer) to the tissue, after which a laser is used toactivate the solder and form a bond. Without wishing to be bound bytheory, it has been reported that the mechanism of laser tissuesoldering appears to include a heating-induced proteindenaturation-renaturation process. See, e.g., B. Forer et al.,Laryngoscope 116: June 2006, 1002-1006.

Solder materials are used in the present disclosure as bonding materialsto bond stent-containing device materials to tissue, for example, by theapplication of heat to a solder material while it is in contact with astent-containing device material (e.g. a stent component material or anoptional covering material) and tissue, such that the stent-containingdevice material is bonded to the tissue. As indicated above, beneficialenergy sources for the application of heat include light sources (e.g.,lasers, etc.), radiofrequency sources (e.g., microwave sources, etc.)and plasma sources (e.g., argon beams, etc.), among others.

Particularly beneficial solder materials have a relatively lowactivation temperature and are bioresorbable. For example, the soldermay be bioresorbed over time, typically between about 4 days and sixmonths (e.g., ranging from 4 days to 1 week to 2 weeks to 1 month to 2months to 3 months to 6 months) (i.e., ranging between any two of thepreceding numerical values), depending on the solder that is used. Thebioresorption rate may be adjustable to provide bioresorption withinthis range, or to sooner than or after this range, by adjusting thechemistry of the solder.

Specific solder materials for use in conjunction with the presentdisclosure include solders of biological origin and synthetic solders.Examples of solders of biological origin include those based onbiological polymers, for example, polypeptides including nano-peptidesand proteins such as albumin, collagen, elastin, fibrin, fibrinogen,thrombin, prothrombin protein derivatives, as well as polysaccharidesincluding chitosan, among others. In some embodiments, two, three, fouror more solder materials such as those described above are employed.Specific examples include a combination of albumin and collagen, acombination of albumin and chitosan, a combination of collagen andchitosan, and a combination of albumin, collagen, and chitosan, amongmany other possible combinations.

Other polymers that may be added include: water soluble or bioresorbablepolymers, for example, synthetic water soluble or bioresorbablepolymers, such as polylactic acid, polyglycolic acid, polydioxanone,polycaprolactone, tyrosine based polyesters, tyrosine basedpolycarbonates, polyesteramides, polyanhydrides, polyhydroxyalkanoates,polyethylene glycols, polyorthoesters, pluronics, such as blockcopolymers of ethylene glycol and propylene glycol, polyamides,polyvinylalcohol, hydroxyl substituted poly(meth)acrylates, polyethyleneglycol substituted (meth)acrylates, (methacrylate-b-polyethers) orcopolymers derived from these monomers, among others. One or more ofthese water soluble or bioresorbable polymers may be mixed with soldersof biological origin, such as those above, to change the properties ofthe solder material. As a specific example, PLGA can be mixed withalbumin to increase the flexibility of the albumin solder.

In some embodiments, at least one energy absorber is used within thesolder material to enhance heating efficiency and/or heat distributionwithin the solder material. Energy absorbers include chromophores, forexample, light-specific dyes such as indocyanine green (ICG),fluorescein, basic fuchsin, and fen, nano-metals such as nano-gold(e.g., gold nanorods, gold nanoshells, gold nanocages, etc.) and SPIONs(superparamagnetic iron oxide nanoparticles), among other materials.Specific examples include ICG-doped albumin, fluorescein-dye-dopedalbumin, and nano-gold-doped albumin, among many others. Metal (e.g.,gold, etc.) or semiconductor nanoparticles, including rods, nanoshells,and other shapes, may be included in the solder material and heated byexcitation at their plasmon frequencies. For further information, see,e.g., Alexander O. Govorov et al, “Generating heat with metalnanoparticles,” Nano Today, Volume 2, Issue 1, February 2007, Pages30-38.

Photochemical tissue bonding processes are known the surgical art. Theseprocesses take advantage of the photochemical reactions that occur atintimately associated tissue surfaces, which are stained with aphotosensitizing dye (e.g., dyed tissue surfaces which are placed incontact with one another). Without wishing to be bound by theory, it isbelieved that the dye absorbs photons of visible radiation and promotesthe formation of covalent bonds between molecules on the approximatedtissue surfaces. For example, reactive species that are produced uponlight activation of the dye can react with potential electron donors andacceptors such as amino acids in proteins (e.g., tryptophan, tyrosine,cysteine, and so forth). In this regard, photochemical methods have beenreported to form crosslinks in collagen type I molecules. See, BarbaraP. Chan et al., Journal of Surgical Research 108, 77-84 (2002).

In certain aspects of the present disclosure, photosensitizing dyes areused to bond stent-containing devices to tissue surfaces, for example,by the application of light of a suitable wavelength to aphotosensitizing dye and a solder material (e.g., a biological soldermaterial, including those set forth above, among others) in intimateassociation with a stent-containing device and a tissue surface (e.g., aphotosensitizing dye admixed with a solder material or coated on asurface of a solder material that is in contact with and disposedbetween a stent-containing device and tissue), such that thestent-containing device is bonded to the tissue. A light-emitting energysource such as a low-power laser or light-emitting diode (LED) may beused for this purpose, among others.

Specific examples of photosensitizing dyes include xanthene dyes such asrose bengal, methylene blue and fluorescein, riboflavin dye (e.g.,riboflavin-5-phosphate), lumichrome dye, lumiflavin dye, Reactive Black5, thiazine dye, naphthalimides (e.g., 1,8-naphthalimide), erythrosine,N-hydroxypyridine-2-(1H)-thione (N-HTP), protoporphyrin I throughprotoporphyrin IX, coproporphyrins, uroporphyrins, mesoporphyrins,hematoporphyrins and sapphyrins, chlorophylis, e.g., bacteriochlorophyllA, Photofrin®, synthetic diporphyrins and dichlorins, phthalocyanineswith or without metal substituents, chloroaluminum phthalocyanine withor without varying substituents, O-substituted tetraphenyl porphyrins,3,1-meso tetrakis (o-propionamido phenyl) porphyrin, verdins, purpurins,tin and zinc derivatives of octaethylpurpurin, etiopurpurin,hydroporphyrins, bacteriochlorins of the tetra(hydroxyphenyl) porphyrinseries (e.g., protoporphyrin I through protoporphyrin IX,coproporphyrins, uroporphyrins, mesoporphyrins, hematoporphyrins andsapphyrins), chlorins, chlorin e6, mono-1-aspartyl derivative of chlorine6, di-1-aspartyl derivative of chlorin e6, tin(IV) chlorin e6,meta-tetrahydroxphenylchlorin, benzoporphyrin derivatives,benzoporphyrin monoacid derivatives, tetracyanoethylene adducts ofbenzoporphyrin, dimethyl acetylenedicarboxylate adducts ofbenzoporphyrin, Diels-Adler adducts, monoacid ring “a” derivative ofbenzoporphyrin, sulfonated aluminum PC, sulfonated AlPc, disulfonated,tetrasulfonated derivative, sulfonated aluminum naphthalocyanines,naphthalocyanines with or without metal substituents and with or withoutvarying substituents, chlorophylis, bacteriochlorophyll A,anthracenediones, anthrapyrazoles, amino anthraquinone, phenoxazinedyes, phenothiazine derivatives, chalcogenapyrylium dyes, cationicselena and tellurapyrylium derivatives, ring-substituted cationic PC,pheophorbide derivative, naturally occurring porphyrins,hematoporphyrin, ALA-induced protoporphyrin IX, endogenous metabolicprecursors, 5-aminolevulinic acid, benzonaphthoporphyrazines, cationicimminium salts, tetracyclines, lutetium texaphyrin, texaphyrin,tin-etio-purpurin, porphycenes, benzophenothiazinium, eosin, erythrosin,cyanines, merocyanine 540, selenium substitued cyanines, flavins,riboflavin, proflavin, quinones, anthraquinones, benzoquinones,naphthaldiimides, victoria blue, toluidine blue, dianthroquinones (e.g.,hypericin), fullerenes, rhodamines and photosensitive derivativesthereof.

An advantage of using light rather than heat is that there is less riskof causing damage to the tissue (cell death) from heat. Anotheradvantage of using light, rather than heat, to achieve device-to-tissuebonding is that complications due to uneven heat distribution can bereduced or eliminated.

In addition, the use of wavelength-specific absorbers such aschromophores enables differential absorption between thechromophore-containing regions and surrounding tissue. One advantage isa selective absorption of radiation by the target, without the need fora precise focusing. Moreover, lower power levels may be used because ofthe increased absorption of chromophore-containing regions, leading toreduced tissue damage.

Stent-containing devices include self-expanding and balloon-expandabledevices. The stent component of the stent-containing device may bemetallic or polymeric, biostable or biodegradable. In certainembodiments, the stent component is formed from a metal selected fromstainless steel, nitinol, titanium and Elgiloy (an alloy comprisingcobalt, chromium and nickel), among others. In certain otherembodiments, the stent portion is formed from a biodegradable polymerselected from polylactide, polyglycolide, poly(lactide-co-glycolide),polycaprolactone, and polydioxanone, among others. In certain additionalembodiments, the stent portion is formed from a biodegradable metal suchas iron, iron alloy, magnesium and magnesium alloy, among others.

The stent struts can be coated with a coating material that does notspan the cells between the struts (coated stent). The stent struts canbe covered by a covering material that spans the cells between the stentstruts (covered stent).

As previously indicated, stent-containing device materials for use inaccordance with the present disclosure include bare stents, drug elutingstents (which may have a drug eluting coating), and stents that arepartially or completely covered by a covering material. Coveringmaterials include non-porous covering materials (e.g., solid films) andporous covering materials, including porous films (e.g., expandedpolytetrafluoroethylene, or ePTFE) and fiber based coverings. In thisregard, stent coverings for use in the present disclosure may be formedusing a variety of fiber-based construction techniques and include, forexample, woven stent coverings and non-woven stent coverings (e.g.,knitted, braided, coiled, randomly wrapped, spunbound, etc.).

Covering materials may be selected from various synthetic and naturalpolymers. Beneficial polymers for forming coverings for stent-containingdevices may be selected from the following, among others: (a)polysiloxanes (i.e., silicones), including polydimethylsiloxane (PDMS),among others, (b) fluoropolymers, including homopolymers and copolymersof C2-C8 alkenes in which one or more hydrogen atoms are substitutedwith fluorine, for example, polytetrafluoroethylene (PTFE),polyvinylidene fluoride (PVDF), poly(vinylidenefluoride-co-hexafluoropropene) (PVDF-HFP), among others, (c) polyamidessuch as nylons, among others, (d) polyesters, including, for example,polyethylene terephthalate, among others, (e) polyurethanes such aspolyether-based polyurethanes, polycarbonate-based polyurethanes, andpolyalkene-based polyurethanes (e.g., polyisobutylene-basedpolyurethanes), among others, (f) polyolefin homopolymers andcopolymers, including homopolymers and copolymers of C2-C8 alkenes, forexample, polyethylene and polypropylene, among others, (g)polyoxyalkylenes including homopolymers of trioxane (e.g., polytrioxane,also known as polyoxymethylene or acetal) and copolymers of trioxane(e.g., copolymers of trioxane and dioxane), and (h) styrenic copolymerssuch as alkene-styrene copolymers, including block copolymers comprisingone or more polystyrene blocks and one or more polyalkene blocks, forinstance, poly(styrene-b-isobutylene-b-styrene) (SIBS) orpoly(styrene-b-ethylene/butylene-b-styrene) (SEBS), among others.

The fiber width (e.g., the diameter of a circular fiber) in afiber-based stent coverings may vary widely. In certain embodiments, thestent-containing devices of the present disclosure may have fiber widthsranging from 1 μm to 500 μm (for example, ranging from 1 μm to 2.5 μm to5 μm to 10 μm to 25 μm to 50 μm to 100 μm to 250 μm to 500 μm) (i.e.,ranging between any two of the preceding numerical values), among othervalues. In certain embodiments, fibers may be provided with surfacefeatures, for example, to increase the surface area of the fibers andthus the contact area between the fibers and a bonding material coating.

Porous stent coverings in accordance with the present disclosure mayalso have a wide range of pore sizes. In various embodiments, thestent-containing devices of the present disclosure may have area poresizes ranging from 1 μm to 100 μm (for example, ranging from 1 μm to 2.5μm to 5 μm to 10 μm to 25 μm to 50 μm to 100 μm) (i.e., ranging betweenany two of the preceding numerical values).

Bonding material may be associated with a stent-containing device invarious ways. For example, bonding material may be applied as a coatingon all or a portion of a bare stent component, applied as a coating onall or a portion of a coated stent (e.g., a drug-eluting stent), orapplied as a coating on all or a portion of a partially or fully coveredstent. As another example, bonding material may be admixed withimpregnated into all or a portion of a stent component material(particularly a polymeric stent material), admixed with impregnated intoall or a portion of a stent coating material, admixed with impregnatedinto all or a portion of a stent covering material, or a combination ofthe foregoing. As another example, a layer (e.g., a sheet) of bondingmaterial may be laminated onto all or a portion of a stent componentmaterial, laminated onto all or a portion of a stent coating material,laminated onto all or a portion of a stent covering material, or acombination of the foregoing. A stent covering material may be coated,impregnated, and/or laminated with a bonding material either before orafter the stent covering material is associated with the stentcomponent.

The bonding material may be present, for example, over the entire lengthof the stent-containing device or only at certain points along thelength of the stent-containing device, for instance, associated with theends of the stent-containing device. This allows potions of thestent-containing device to be largely free of bonding material, whichreduces bonding material consumption, among other advantages.

Bonding material may be impregnated into and/or coated onto anothermaterial using various techniques which may be selected, for example,from dipping techniques, spraying techniques, spin coating techniques,web coating techniques, electrostatic techniques, techniques in whichbonding material is selectively applied to certain regions of thestent-containing device but not others, for example, through the use ofa suitable application device such as a sprayer, brush, roller, pen, orprinter (e.g., screen printing device, ink jet printer, etc.).

If the bonding material does not adhere to the stent, the (optional)covering material, or both, an intermediate layer that bonds to (a) thebonding material and (b) the stent, the (optional) covering material, orboth, may be used, for example, as a tie layer. In certain embodiments,the intermediate layer may be transparent to the energy that is appliedto the bonding material.

As previously indicated, various embodiments of the present disclosurepertain to stent-containing devices in which the stent component may be,for example, metallic or polymeric, biostable or bioresorbable,self-expanding or balloon expandable.

In some embodiments, a stent component may be formed entirely of bondingmaterial.

In some embodiments, a stent component is partially or fully coated orimpregnated with bonding material.

In some embodiments, the bonding material may be bioresorbable, forexample, leaving nothing but the stent component and/or optionalcovering material behind after integration (e.g., where the stent oroptional covering material is biostable or bioresorbable). As notedabove, the rate of bioresorption may be adjusted, for example, from daysto weeks to months.

In some embodiments, the stent component elements (e.g., stent wire,stent struts, etc.) can be coated in bonding material, leaving the cellsopen. One specific embodiment is shown in FIG. 1, which shows a stent100, whose structural elements are completely coated with a bondingmaterial 120, but in which the stent cells 110 c are left open.

In other embodiments, the bonding material may cover the stent cells. Aspecific embodiment is shown in FIG. 2, which is a schematicillustration of a stent 100, whose stent cells are covered with bondingmaterial 120. The bonding material may be, for example, only on theouter (abluminal) surface of the structural elements 110, only on theinner (luminal) surface of the structural elements 110, or maycompletely enclose the structural elements 110.

In some embodiments, the stent is partially coated or impregnated withbonding material. A specific embodiment is schematically shown in FIG.3, which shows a stent 100, wherein the bonding material 120 is appliedto structural elements 110 only at the ends of the stent. Anotherspecific embodiment is schematically shown in FIG. 4, wherein thebonding material 120 is applied to structural elements 110 at intervalsalong the length of the stent 100. In the embodiments shown in FIGS. 3and 4, bonding material 120 spans at least portions of the stent cells.The bonding material 120 may be, for example, only on the outer(abluminal) surface of the structural elements 110, only on the inner(luminal) surface of the structural elements 110, or may completelyenclose the structural elements 110. In other embodiments, thestructural elements are coated with bonding material, leaving the stentcells open.

In some embodiments, stent-containing devices are provided wherein astent component is partially or fully covered with a covering material.As elsewhere, the stent component may be metallic or polymeric, biostable or bioresorbable, self-expanding or balloon expandable. Thecovering material may be biostable or bioresorbable, porous ornon-porous. The covering material may be a woven or non-woven fibrousconstruct. The covering material may fully or partially cover the stentcomponent.

A partially or fully covered stent may, in turn, be partially or fullycoated with a bonding material. For example, a partially or fullycovered stent may be coated with a bonding material on the outside(abluminal) surface, but not the inside (luminal) surface. A partiallyor fully covered stent may be coated with bonding material at or nearthe ends of the stent, or in any other strategic areas. A partially orfully covered stent may be coated with bonding material on the coveringbut not on the stent component.

A specific embodiment is schematically shown in FIG. 5A, wherein onlythe central area of the stent portion is covered in a covering material130. Bonding material 120 is applied to structural elements 110 at theends of the stent in the areas that are not covered in the coveringmaterial 130. In the embodiment shown, bonding material 120 spans thestent cells, in which case the bonding material 120 may be present, forexample, only on the outer (abluminal) surface of the structuralelements 110, only on the inner (luminal) surface of the structuralelements 110, or may completely enclose the structural elements 110. Inother embodiments, the structural elements are coated with bondingmaterial, leaving the stent cells open.

Another specific embodiment is schematically shown in FIG. 5B, whereinthe entire stent is covered in a covering material 130 and bondingmaterial 120 is applied to the covering material at the ends of thestent. In certain embodiments, the covering material may be made of amaterial that is transparent to the bonding energy that is applied, suchthat bonding energy from an energy source positioned luminally relativeto the covering material (i.e., inside the stent) can reach bondingmaterial on the outer (abluminal) surface of the covering material. Ifan intermediate layer (not shown) is disposed between the bondingmaterial 120 and the covering material 130, the intermediate materialmay be made of a material that is transparent to the bonding energy thatis applied as well.

In certain embodiments, for example, as shown in FIG. 6, the coveringmaterial 130 may be have openings of varying size to allow the energy topass through covering and activate the bonding material 120. The bondingmaterial 120 may span the holes as shown, and may also be applied to allor a portion of the covering material 130 in some embodiments. In someembodiments, the structural elements 110 are coated with bondingmaterial, but the stent cells are left open.

In some embodiments, bonding material is applied to the siteindependently of the stent-containing device, in which case thestent-containing device either may be associated with bonding materialat the time of delivery (see, e.g., FIGS. 1-6) or may be free of bondingmaterial at the time of delivery. In these embodiments, the bondingmaterial may be applied to tissue followed by delivery of thestent-containing device, or the stent-containing device may be deliveredfollowed by application of the bonding material. After introduction ofthe device and bonding material, the device and bonding material areirradiated using a suitable energy source.

The independently applied bonding material may be applied in solid form,fluid form or a combination thereof. Where independently deposited insolid form, the bonding material may be, for example, in the form of apatch or in a film or tape mounted onto a device suitable for radialexpansion (e.g., a balloon) that can be pressed against a lumen wall byexpanding the device (e.g., by inflating the balloon). Whereindependently deposited the form of a fluid, the bonding material maybe, for example, in the form of a liquid, paste or gel (e.g., an organicor aqueous liquid, paste or gel comprising a solider material and/orphotosensitizing dye), which is deposited using a suitable device suchas a catheter. For example, the bonding material may be applied via acatheter to a body lumen prior to deployment of the stent-containingdevice or the bonding material may be deposited onto thestent-containing device after deployment via a catheter. The bondingmaterial and stent-containing device are then irradiated via a suitableenergy source, for example, using an energy source integrated into thedepositing catheter or another means.

In certain embodiments, bonding material may be applied to a body lumenwithout implanting a stent-containing device. Where deposited in thesolid form, the bonding material may be, for example, in the form of apatch or in a film or tape mounted onto a device suitable for radialexpansion. Once pressed against the lumen wall, the bonding material maythen be welded to the wall by exposing it to energy. This may be used,for example, to repair and/or seal tears in the lumen. In otherembodiments, a bonding material in fluid form may be used to repairand/or seal tears in the lumen.

As previously noted, a variety of energy sources may be employed in thepresent disclosure. In some embodiments, the energy source is providedin conjunction with its own independent device, whereas in otherembodiments, the energy source may integrated into a delivery device. Invarious embodiments, the energy source is adapted to radially directenergy outward from the side of the device. In certain cases, the energysource is rotatable (e.g., manually or mechanically), allowing energy tobe directed in a full circle (i.e., 360° irradiation). Full circleirradiation may be also achieved, for example, by directing energy fromaround the entire circumference of the device (e.g., by means ofmultiple LED's, multiple optical fibers, etc.). In certain embodiments,energy is directed from the energy source through a transparentmaterial, for example, a transparent hollow catheter shaft or atransparent balloon, among other possibilities.

In embodiments where the energy source is provided in conjunction withits own independent device, the energy source may be, for example,integrated into an over-the-wire or monorail catheter, or the energysource may also be inserted, for example, through a lumen in a deliverycatheter. In one embodiment, illustrated in FIG. 10, a light emittingdevice 340 may be provided with multiple light emitting elements 340 e,for example, multiple LEDs or fiber optic termini, which radiateoutwardly from the device.

As an example of an embodiment where the energy source is integratedinto a delivery device, the energy source may be integrated into a guidewire 345 as shown in FIG. 11, for instance, by using providing a guidewire with a light emitting fiber optic core 345 e. Light from the coremay be radially dispersed at the point where the light emerges from thecore using a suitable optical element. In certain other embodiments, theenergy course is integrated into a delivery catheter. For example, thedelivery catheter may be provided with multiple LEDs or fiber optictermini which radiate outwardly from the delivery catheter. In someembodiments, an energy source is provided in conjunction with a ballooncatheter, in which case an energy source 360 e may be mounted distal tothe balloon 365 of the balloon catheter 360 as shown in FIG. 12. Theenergy source may also be positioned proximal to the balloon or withinthe balloon. If positioned within the balloon, the balloon is made froma material that is transparent to the energy being irradiated. Anadvantage in providing the energy source within a balloon, is that theballoon helps to keep the energy source centered in the body lumen. Ofcourse, mechanisms other than a balloon can be used to center the energysource, such as a delivery sheath or a stent.

An embodiment of a procedure for delivering a stent in accordance withthe present disclosure will now be described in conjunction with FIGS.7A-7C. Initially, a guide wire 310 is positioned in a body lumen 200 asshown in FIG. 7A. Then a stent is delivered over the guide wire 310. Forexample, a stent may be delivered using a delivery device as known inthe stent delivery art, for example, a device in which the stent ispositioned between an outer catheter sheath 330 and an inner cathetermember 320 and delivered to a delivery site whereupon the sheath 330retracted, leading to self-expansion of the stent as shown in FIG. 7B.Unlike other known procedures, however, the stent in the presentembodiment is one in which the stent elements 110 are coated with abonding material 120 at the ends of the stent. In the embodiment shown,after the stent is delivered, the delivery catheter is withdrawn and adevice 340 with an energy emitting element 340 e is introduced over theguide wire 310, allowing the bonding material 120 to be activated andthe stent to be fixed to the tissue of the body lumen 200. In otherembodiments, an energy source may be included in the delivery catheter.

Another embodiment of a procedure for delivering a stent in accordancewith the present disclosure will now be described in conjunction withFIGS. 8A-8C. In this embodiment, a first catheter 350 having a firstballoon 355 is positioned in a body lumen 200 as shown in FIG. 8A,blocking flow within the body lumen 200, which may be, for example, ablood vessel. Then a stent 100 is delivered to the site, loaded on asecond catheter 360 that is advanced over the first catheter 350 asshown in FIG. 8B. In the embodiment shown, the entire length of thestent 100 is provided with bonding material. As seen in FIG. 8C, thesecond catheter 360 has a second balloon 365 which expands the stent 100in the body lumen 200 upon inflation. After stent expansion, an energysource within the balloon 365 of the second catheter 360 may be used toactivate the bonding material in the stent 100, allowing the stent to befixed to tissue of the body lumen 200. In other embodiments, the energysource is introduced via a separate device.

Yet another embodiment of a procedure for delivering a stent inaccordance with the present disclosure will now be described inconjunction with FIG. 9. In this embodiment a self-expanding or balloonexpandable stent having stent elements 110 and a stent covering 130 isdelivered to a body lumen 200 using a suitable delivery technique (e.g.,via a catheter with a retractable sheath, a balloon catheter, etc.).Subsequently, a catheter 370 is used to deliver bonding material to thestent. For example, as shown in FIG. 9, bonding material 120 may bedelivered in liquid form from one or more lumens 370 l in the deliverycatheter 370. After application of the bonding material 120, the stentand tissue are illuminated via a suitable energy source 370 e, which issupplied on the catheter 370 in this embodiment, thereby activating thebonding material 120 such that the stent is bonded to the tissue of thebody lumen 200. In other embodiments, the energy source is inserted viaa separate device.

In certain embodiments, the stent-containing devices of the presentdisclosure may comprise various additional agents, including therapeuticagents and imaging agents, among other possible agents. Such agents maybe included, for example, in a coating on or incorporated into all or aportion of the stent component material, in a coating on or incorporatedinto all or a portion of the bonding material and/or as a coating on orincorporated into all or a portion of the optional covering material.

“Therapeutic agents,” drugs,” “bioactive agents” “pharmaceuticals,”“pharmaceutically active agents” and other related terms may be usedinterchangeably herein. Therapeutic agents include anti-restenosis,anti-hyperplasic and anti-granulation tissue agents. Therapeutic agentsmay be used singly or in combination.

Additional agents for use in conjunction with the stent-containingdevices of the present disclosure also include imaging agents including(a) contrast agents for use in connection with x-ray fluoroscopy,including metals, metal salts and oxides (particularly bismuth salts andoxides), and iodinated compounds, among others, (b) contrast agents foruse in conjunction with ultrasound imaging, including organic andinorganic echogenic particles (i.e., particles that result in anincrease in the reflected ultrasonic energy) or organic and inorganicecho lucent particles (i.e., particles that result in a decrease in thereflected ultrasonic energy), and (c) contrast agents for use inconjunction with magnetic resonance imaging (MRI), including contrastagents that contain elements with relatively large magnetic moment suchas God(III), MN(II), Fe(III) and compounds (including chelates)containing the same, such as gadolinium ion chelated withdiethylenetriaminepentaacetic acid.

In various embodiments, the stent-containing devices may contain fromless than 1 wt % to 50 wt % or more of one or more of the precedingadditional agents.

In another aspect of the disclosure, medical kits useful instent-containing device procedures are provided. The medical kits mayinclude all or a subset of all the components useful for performing theprocedures. For example, the medical kits may comprise any combinationof any two, three, four, or more of the following items: (a) astent-containing device, either without or with an associated bondingmaterial, (b) a bonding material, for example, in fluid form or solidform, (c) one or more medical devices (e.g., a guide wire, a stentdelivery device, and/or a device that is used to apply bondingmaterial), (d) an energy source (e.g., in a stand-along unit orassociated with a surgical instrument), (e) suitable packaging material,and (f) printed material with one or more of the following: (i) storageinformation and (ii) instructions regarding how to implant thestent-containing device in a subject.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent disclosure are covered by the above teachings and are within thepurview of the appended claims without departing from the spirit andintended scope of the invention.

What is claimed is:
 1. A medical device comprising: a stent body havingtwo ends, a central region therebetween, and comprising structuralelements extending around the stent body; and a covering materialdisposed over the stent body, the covering material covering only aportion of the stent body; wherein the covering material is providedwith a plurality of openings that provide areas where the stent body isnot covered by the covering material.
 2. The medical device of claim 1,wherein the covering material comprises: (a) polysiloxanes; (b)fluoropolymers; (c) polyamides; (d) polyesters; (e) polyurethanes; (f)polyolefin polymers; (g) polyoxyalkylenes; or (h) styrenic copolymers;(i) any combinations one or more of the foregoing (a)-(h).
 3. Themedical device of claim 1, wherein the plurality of openings aredisposed around a circumference of the stent body.
 4. The medical deviceof claim 1, comprising a bonding material associated with the structuralelements, wherein the bonding material is associated with the structuralelements at least in areas of the stent body not covered by the coveringmaterial.
 5. The medical device of claim 4, wherein the bonding materialis associated with the structural elements only in areas of the stentbody not covered by the covering material.
 6. The medical device ofclaim 4, wherein the bonding material is configured to bond to tissuewhen the bonding material is exposed to an energy source.
 7. The medicaldevice of claim 6, wherein the energy source is selected from a lightenergy source, a microwave energy source, a radio frequency energysource, infrared energy source, radiation source, and a plasma energysource.
 8. The medical device of claim 4, wherein the bonding materialis associated with the medical device by integrating the bondingmaterial into at least a portion of the structural elements.
 9. Themedical device of claim 1, wherein the medical device is self-expandingor balloon-expandable.
 10. A method of treatment: inserting into a bodylumen a medical device that comprises a stent body having two ends, acentral region therebetween, and comprising structural elementsextending around the stent body; and a covering material disposed overthe stent body, the covering material covering only a portion of thestent body, wherein the covering material is provided with a pluralityof openings that provide areas where the stent body is not covered bythe covering material; deploying the stent body in the body lumen suchthat the medical device contacts a tissue wall of the body lumen. 11.The method of claim 10, wherein the covering material comprises: (a)polysiloxanes; (b) fluoropolymers; (c) polyamides; (d) polyesters; (e)polyurethanes; (f) polyolefin polymers; (g) polyoxyalkylenes; or (h)styrenic copolymers; (i) any combinations one or more of the foregoing(a)-(h).
 12. The method of claim 10, wherein the plurality of openingsare disposed around a circumference of the stent body.
 13. The method ofclaim 10, wherein the stent comprises a bonding material associated withthe structural elements, wherein the bonding material is associated withthe structural elements at least in areas of the stent body not coveredby the covering material and wherein the method comprises bonding thebonding material to the tissue wall.
 14. The method of claim 13, whereinbonding the bonding material to the tissue wall comprises exposing thebonding material to an energy source selected from a light energysource, a microwave energy source, a radio frequency energy source,infrared energy source, radiation source, and a plasma energy source.15. A medical apparatus, comprising: (a) medical device comprising astent body having two ends, a central region therebetween, andcomprising structural elements extending around the stent body; and acovering material disposed over the stent body, the covering materialcovering only a portion of the stent body, wherein the covering materialis provided with a plurality of openings that provide areas where thestent body is not covered by the covering material; and (b) ballooncatheter or a catheter having a retractable sheath configured to deliverthe medical apparatus.
 16. The medical apparatus of claim 15, whereinthe covering material comprises: (a) polysiloxanes; (b) fluoropolymers;(c) polyamides; (d) polyesters; (e) polyurethanes; (f) polyolefinpolymers; (g) polyoxyalkylenes; or (h) styrenic copolymers; (i) anycombinations one or more of the foregoing (a)-(h).
 17. The medicalapparatus of claim 15, wherein the plurality of openings are disposedaround a circumference of the stent body.
 18. The medical apparatus ofclaim 15, wherein the medical device comprises a bonding materialassociated with the structural elements at least in areas of the stentbody not covered by the covering material.
 19. The medical apparatus ofclaim 18, wherein the apparatus further comprises an energy source andwherein the medical device is configured to bond to tissue when thebonding material is exposed to the energy source.
 20. The medicalapparatus of claim 19, wherein the energy source is selected from alight energy source, a microwave energy source, a radio frequency energysource, infrared energy source, radiation source, and a plasma energysource.